Process for producing organic compound having nitroxide free radical

ABSTRACT

An organic compound having a nitroxide free radial of the formula (2) is prepared by reacting a cyclic secondary amine having a steric hindrance of the formula (1) with a peroxide in the presence of at least 1 part by weight of an organic compound having a cyano group per 1 part by weight of the cyclic secondary amine having the steric hindrance. In the formulae (1) and (2), T is a methylene group, an ethylene group, an oxygen atom or a methyleneoxy group; R is an alkyl group, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxy group, an acyl group an acyloxy group, an amino group, a hydroxyl group or a heterocyclic group; R 1 , R 2 , R 3  and R 4  are the same or different and each an alkyl group or an aryl group, or R 1  and R 2  and/or R 3  and R 4  together form a tetramethylene group or a pentamethylene group; and n is an integer of 0 to 6.

This application is a 371 application of PCT/JP99/07379 filed Dec. 28,1999.

FIELD OF THE INVENTION

The present invention relates to a process for preparing an organiccompound having a nitroxide free radial of the formula (2):

wherein T is a methylene group, an ethylene group, an oxygen atom or amethyleneoxy group; R is an alkyl group, an aralkyl group, an arylgroup, a cycloalkyl group, an alkoxy group, an acyl group an acyloxygroup, an amino group, a hydroxyl group or a heterocyclic group; R¹, R²,R³ and R⁴ are the same or different and each an alkyl group or an arylgroup, or R¹ and R² and/or R³ and R⁴ together form a tetramethylenegroup or a pentamethylene group; and n is an integer of 0 to 6. Thiscompound will be referred to as the “nitroxide compound (2)”.

The nitroxide compound (2) is useful as a spin label or a spin probeused in the ESR spectrum analysis, a polymerization inhibitor forunsaturated compound, or a stabilizer of organic polymers againstthermal decomposition and photochemical decomposition.

BACKGROUND ART

It is known that an organic compound having a nitroxide free radicalsuch as the nitroxide compound (2) is prepared by oxidizing a secondaryamine having a steric hindrance with a peroxide. That is, the nitroxidecompound (2) can be prepared by oxidizing a cyclic secondary aminehaving a steric hindrance of the formula (1):

wherein T, R, R¹, R², R³, R⁴ and n are the same as defined above with aperoxide.

However, when 2,2,6,6-tetramethylpiperidine is used as a cyclicsecondary amine (1) and it is oxidized to obtain2,2,6,6-tetramethylpiperidine-N-oxyl, industrially satisfactory resultsare not attained, for example, the yield of the desired product is lowas understood from the result of Comparative Examples described below,and the reaction time is long.

DISCLOSURE OF THE INVENTION

One object of the present invention is to provide a process forpreparing the nitroxide compound (2) by oxidizing the cyclic secondaryamine (1) with a peroxide at a high yield in a short reaction time.

The present inventors have made extensive study to solve the aboveproblems. As a result, it has been found that the nitroxide compound (2)can be obtained at a high yield in a short reaction time, when thecyclic secondary amine (1) is reacted with the peroxide in the presenceof at least 1 wt. part of an organic compound having a cyano group per 1wt. part of the cyclic secondary amine (1), and the present inventionhas been completed.

Accordingly, the present invention provides a process for preparing thenitroxide compound (2) comprising the step of reacting a cyclicsecondary amine of the formula (1):

with a peroxide in the presence of at least 1 wt. part of an organiccompound having acyano group per 1 wt. part of the cyclic secondaryamine (1).

EMBODIMENTS FOR CARRYING OUT THE INVENTION

The present invention will be explained in detail.

In the above formula (1), which represents the cyclic secondary amineused in the process of the present invention, T is a methylene group, anethylene group, an oxygen atom or a methyleneoxy group; R is an alkylgroup, an aralkyl group, an aryl group, a cycloalkyl group, an alkoxygroup, an acyl group an acyloxy group, an amino group, a hydroxyl groupor a heterocyclic group; R¹, R², R³ and R⁴ are the same or different andeach an alkyl group or an aryl group, or R¹ and R² and/or R³ and R⁴together form a tetramethylene group or a pentamethylene group; and n isan integer of 0 to 6.

The alkyl group represented by R may be a linear or branched alkyl grouphaving 1 to 6 carbon atoms. Specific examples of the alkyl group includea methyl group, an ethyl group, a n-propyl group, an isopropyl group, an-butyl group, an isobutyl group, a n-pentyl group, an isopentyl group,a neopentyl group, a n-hexyl group, a 2-methylpentyl group, a3-methylpentyl group, a neohexyl group, etc.

The aralkyl group may be an aralkyl group having 7 to 15 carbon atoms.Specific examples of the aralkyl group include a benzyl group, aphenethyl group, a phenylpropyl group, a benzhydryl group, etc.

Specific examples of the aryl group include a phenyl group, a tolylgroup, a xylyl group, a naphthyl group, etc.

The cycloalkyl group may be a cycloalkyl group having 3 to 8 carbonatoms. Specific examples of the cycloalkyl group include a cyclopropylgroup, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, acycloheptyl group, a cyclooctyl group, etc.

Specific examples of the alkoxy group include alkyloxy groups (e.g. amethoxy group, an ethoxy group, a propoxy group, etc.), and aralkyloxygroups (e.g. a benzyloxy group, etc.) Specific examples of the acylgroup include linear or branched lower alkanoyl groups having 1 to 6carbon atoms (e.g. a formyl group, an acetyl group, a propionyl group, abutyryl group, a valeryl group, a pivaloyl group, a pentanoyl group,etc.) and aroyl groups (e.g. a benzoyl group, a toluoyl group, a xyloylgroup, a naphthoyl group, etc.)

Specific examples of the acyloxy group include alkanoyloxy gropus (e.g.an acetoxy group, a propionyloxy group, etc.) and aroyloxy groups (e.g.a benzoyloxy group, etc.)

Specific examples of the heterocyclic group include a thienyl group, apyrrolyl group, a pyranyl group, a thiopyranyl group, a pyridyl group, athiazolyl group, an imidazolinyl group, a pyrimidinyl group, a triazinylgroup, an indolyl group, a quinolyl group, a purinyl group, abenzothiazolyl group, etc.

R in the formula substitutes a hydrogen atom on the ring of the cyclicsecondary amine (1)

Examples of the alkyl and aryl groups represented by R¹, R², R³ and R⁴may be the same as those exemplified in connection with R. Preferably,R¹, R², R³ and R⁴ are methyl groups.

Specific examples of the cyclic secondary amine (1) include2,2,5,5-tetramethylpyrrolidine; derivatives of2,2,5,5-tetramethylpyrrolidine which have a substituent such as analkoxy group (e.g. a methoxy group, an ethoxy group, a propoxy group,abenzyloxygroup, etc.), anacyloxygroup (e.g. anacetoxy group, apropionyloxy group, a benzoyloxy group, etc.) or a hydroxyl group on the3-position of 2,2,5,5-tetramethylpyrrolidine;2,2,6,6-tetramethylpiperidine; derivatives of2,2,6,6-tetramethylpiperidine which have a substituent such as an alkoxygroup (e.g. a methoxy group, an ethoxy group, a propoxy group, abenzyloxy group, etc.), an acyloxy group (e.g. an acetoxy group, apropionyloxy group, a benzoyloxy group, etc.) or a hydroxyl group on the4-position of 2,2,6,6-tetramethylpiperidine; derivatives of4,4-dimethyloxazolidine such as 2,2,4,4-tetramethyloxazolidine,2,4,4-trimethyl-2-phenyloxazolidine, 4-aza-3,3-dimethyl-1-oxaspiro [4.5]decane, etc.; 3,3,5,5-tetramethylmorpholine; derivatives of3,3,5,5-tetramethylmorpholine which have a substituent such as an alkylgroup (e.g. a methyl group, etc.) on the 2-position of3,3,5,5-tetramethylmorpholine. The cyclic secondary amine (1) may not belimited to the above exemplified compounds.

According to the process of the present invention, the nitroxidecompound (2) corresponding to the above cyclic secondary amine (1) canbe obtained. For example, 2,2,5,5-tetramethylpyrrolidine-N-oxyl and itsderivatives are prepared from 2,2,5,5-tetramethylpyrrolidine and itsderivatives, 2,2,6,6-tetramethylpiperizine-N-oxyl and its derivativesare prepared from 2,2,6,6-tetramethylpiperizine and its derivatives,4,4-dimethyloxazolidine-N-oxyl derivatives are prepared from4,4-dimethyloxazolidine derivatives, and3,3,5,5-tetramethylmorpholine-N-oxyl and its derivatives are preparedfrom 3,3,5,5-tetramethylmorpholine and its derivatives.

As the peroxide used in the process of the present invention, hydrogenperoxide and any organic peroxide such as hydroperoxide and peracids maybe used. Among them, hydrogen peroxide is preferable from the viewpointof costs and the reduction of the amount of wastes.

When hydrogen peroxide is used, a 5-70 wt. % aqueous solution,preferably a 20-50 wt. % aqueous solution of hydrogen peroxide is used.The amount of hydrogen peroxide is at least 1.5 moles, preferably from1.6 to 3.5 moles per 1 mole of the cyclic secondary amine (1).

In the process of the present invention, the reaction is carried out inthe presence of at least 1 wt. parts, preferably 1.5 to 50 wt. parts,more preferably 2 to 30 wt. parts of an organic compound having a cyanogroup per 1 wt. parts of the cyclic secondary amine (1). Morepreferably, the reaction is carried out in the presence of at least 1.5moles, preferably 2 to 50 moles of the organic compound having the cyanogroup per 1 mole of the cyclic secondary amine group (1) in the aboveweight parts range.

The organic compound having the cyano group is not limited except thosehaving a polymerizable double bond in the molecule such asacrylonitrile. Preferable examples of the organic compound having thecyano group include aliphatic nitrites (e.g. acetonitrile,propionitrile, butyronitrile, valeronitrile, capronitrile, etc.) andaromatic nitrites (e.g. benzonitrile, tolunitrile, etc.)

When hydrogen peroxide is used in the form of an aqueous solution, theorganic compound having the cyano group is preferably a water-solubleone, particularly preferably an acetonitrile and/or propionitrile.

The process of the present invention may be carried out in a solvent.The solvent is suitably selected depending on the kinds of the cyclicsecondary amine (1), the organic compound having the cyano group and thenitroxide compound (2), and preferably selected from solvents which aregood solvents for the cyclic secondary amine (1) and the nitroxidecompound (2), and miscible with the organic compound having the cyanogroup. Examples of the solvent include water, alcohols (e.g. methanol,ethanol, propanol, butanol, isopropanol, etc.), aromatic hydrocarbons(e.g. benzene, toluene, xylene, mesitylene, etc.), ethers (e.g. diethylether, diisopropyl ether, tetrahydrofuran, etc.) and so on. Preferredsolvents are those which are not oxidized with the nitroxide compound(2), for example, water, the aromatic hydrocarbons, the ethers, etc.

The solvent may not be used when the amount of the organic compoundhaving the cyano group is at least 2.5 wt. parts, preferably at least 3wt. parts per 1 wt. parts of the cyclic secondary amine (1), since theorganic compound having the cyano group serves as a solvent in theprocess of the present invention.

A catalyst may be used in the process of the present invention. Thecatalyst may be one that is used in a known process for preparing acompound having a nitroxide free radical by oxidizing a correspondingsecondary amine having a steric hindrance with a peroxide. Preferredexamples of the catalyst are compounds comprising metal elements of the6 Group of the 18 Groups Periodic Table, for example, tungsten,molybdenum, etc. Specific examples of the tungsten compound includetungstic acid, phosphortungstic acid, paratungstic acid, and theiralkali metal salts (e.g. sodium salts, potassium salts) or ammoniumsalts. Specific examples of the molybdenum compounds include molybdicacid, molybdenum oxide, molybdenum carbonyl and their alkali metal salts(e.g. sodium salts, potassium salts) or ammonium salts). Specificexamples include ammonium paratungstate, sodium tungstate,phosphortungstic acid, sodium molybdate, molybdenum trioxide, molybdenumhexacarbonyl, etc.

The amount of the catalyst is usually from 0.001 to 0.1 wt. %,preferably from 0.01 to 0.05 wt. % of the weight of the cyclic secondaryamine (1).

The procedure of the process according to the present invention will beexplained. For example, the peroxide is added to the mixture of thecyclic secondary amine (1) and the organic compound having the cyanogroup while stirring to react the cyclic secondary amine and theperoxide.

The reaction temperature is usually from 0 to 75° C., preferably from 40to 65° C.

The nitroxide compound (2) can be prepared at ahigher yield by the abovemanner in which the reaction proceeds while the peroxide is added,although the cyclic secondary amine (1), the organic compound having thecyano group and the peroxide are mixed and reacted at the abovetemperature while stirring.

The addition time of the peroxide is not limited, and usually from 1 to10 hours, preferably from 3 to 6 hours. After the addition of theperoxide, the reaction mixture is maintained at the above temperaturefor 1 to 10 hours to complete the reaction.

After the completion of the reaction, the nitroxide compound (2) may beisolated from the reaction mixture by a suitable combination of unitprocedures such as concentration, extraction, distillation,recrystallization, etc.

EXAMPLES

The present invention will be illustrated by the Examples, which do notlimit the present invention in any way.

Example 1

In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (4.3 g), acetonitrile(38.6 g) and ammonium paratungstate (0.21 g) were charged, and 35%aqueous hydrogen peroxide (8.8 g) was dropwise added to the mixture over3 hours while stirring and maintaining the temperature at 50 to 51° C.,followed by further reaction while stirring at the same temperature for3 hours. After the completion of the reaction, the reaction mixture wasanalyzed with gas chromatography. The yield of2,2,6,6-tetramethylpiperidine-1-oxyl was 93.5% (based on2,2,6,6-tetramethylpiperidine).

Example 2

A reaction was carried out in the same manner as in Example 1 exceptthat a half of acetonitrile (19.3 g) was replaced by tetrahydrofuran(19.3 g). As a result, the yield of 2,2,6,6-tetramethylpiperidine-1-oxylwas 92.3% (based on 2,2,6,6-tetramethylpiperidine).

Example 3

In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (8.5 g), acetonitrile(25.5 g) and ammonium paratungstate (0.42 g) were charged, and 35%aqueous hydrogen peroxide (17.5 g) was dropwise added to the mixtureover 3 hours while stirring and maintaining the temperature at 50 to 51°C., followed by further reaction while stirring at the same temperaturefor 3 hours. After the completion of the reaction, the reaction mixturewas analyzed with gas chromatography. The yield of2,2,6,6-tetramethylpiperidine-1-oxyl was 90.1% (based on2,2,6,6-tetramethylpiperidine).

Example 4

In a 100 ml reactor, 2,2,6,6-tetramethylpiperidine (8.5 g), acetonitrile(12.8 g), methanol (12.8 g) and ammonium paratungstate (0.42 g) werecharged, and 35% aqueous hydrogen peroxide (17.5 g) was dropwise addedto the mixture over 3 hours while stirring and maintaining thetemperature at 50 to 51° C., followed by further reaction while stirringat the same temperature for 3 hours. After the completion of thereaction, the reaction mixture was analyzed with gas chromatography. Theyield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 71.2% (based on2,2,6,6-tetramethylpiperidine).

Example 5

A reaction was carried out in the same manner as in Example 3 exceptthat no ammonium paratungstate was used. As a result, the yield of2,2,6,6-tetramethylpiperidine-1-oxyl was 94.4% (based on2,2,6,6-tetramethylpiperidine).

Example 6

A reaction was carried out in the same manner as in Example 5 exceptthat the amount of hydrogen peroxide was changed to 11.7 g and theaddition time of hydrogen peroxide was changed to 2 hours. As a result,the yield of 2,2,6,6-tetramethylpiperidine-1-oxyl was 93.1% (based on2,2,6,6-tetramethylpiperidine).

Comparative Example 1

A reaction was carried out in the same manner as in Example 1 exceptthat the amount of acetonitrile was changed to 2.5 g and methanol (36.1g) was used. As a result, the yield of2,2,6,6-tetramethylpiperidine-1-oxyl was 52.0% (based on2,2,6,6-tetramethylpiperidine).

Comparative Example 2

A reaction was carried out in the same manner as in Example 1 exceptthat tetrahydrofuran (38.6 g) was used in place of acetonitrile (38.6g), and the reaction was continued for 10 hours while stirring after thecompletion of the addition of hydrogen peroxide. As a result, the yieldof 2,2,6,6-tetramethylpiperidine-1-oxyl was 38.5% (based on2,2,6,6-tetramethylpiperidine).

The conditions and the results of Examples and Comparative Examples aresummarized in the following Table.

TABLE 1 TMPPR 35% H₂O₂ CH₃CN Solvent Catalyst Yield g (mole) g (mole) g(mole) g g % Ex. 1 4.3(0.03) 8.8(0.09) 38.6(0.94) 0 0.21 93.5 C. Ex. 14.3(0.03) 8.8(0.09) 2.5(0.47) CH₃OH 0.21 52.0 36.1 Ex. 2 4.3(0.03)8.8(0.09) 19.3(0.47) THF 0.21 92.3 19.3 C. Ex. 2 4.3(0.03) 8.8(0.09) 0THF 0.21 38.5 38.6 Ex. 3 8.5(0.06) 17.5(0.18) 25.5(0.62) 0 0.42 90.1 Ex.4 8.5(0.06) 17.5(0.18) 12.8(0.31) CH₃OH 0.42 71.2 12.8 Ex. 5 8.5(0.06)17.5(0.18) 25.5(0.62) 0 0 94.4 Ex. 6 8.5(0.06) 11.7(0.12) 25.5(0.62) 0 093.1

What is claimed is:
 1. A process for preparing an organic compoundhaving a nitroxide free radical of the formula (2):

wherein T is a methylene group, an ethylene group, an oxygen atom or amethyleneoxy group; R is an alkyl group, an aralkyl group, an arylgroup, a cycloalkyl group, an alkoxy group, an acyl group an acyloxygroup, an amino group, a hydroxyl group or a heterocyclic group; R¹, R²,R³ and R⁴ are the same or different and each is an alkyl group or anaryl group, or R¹ and R² and/or R³ and R⁴ together form a tetramethylenegroup or a pentamethylene group; and n is an integer of 0 to 6,comprising the step of reacting a cyclic secondary amine having a sterichindrance of the formula (1):

wherein T, R, R¹, R², R³, R⁴ and n are the same as defined above with aperoxide in the presence of at least 1 part by weight of an organiccompound having a cyano group per 1 part by weight of the cyclicsecondary amine (1).
 2. The process according to claim 1, wherein thereaction is carried out in the presence of a catalyst.
 3. The processaccording to claim 2, wherein said catalyst is a compound comprising ametal element of the 6 Group of the 18 Groups Periodic Table.
 4. Theprocess according to claim 1, wherein said peroxide is hydrogenperoxide.
 5. The process according to claim 2, wherein said peroxide ishydrogen peroxide.
 6. The process according to claim 3, wherein saidperoxide is hydrogen peroxide.